5JP2

Fcho1 Mu homology domain (Danio Rerio) with bound Eps15 peptide

Summary for 5JP2

• Entry DOI: 10.2210/pdb5jp2/pdb
• Descriptor: Epidermal growth factor receptor substrate 15, F-BAR domain only protein 1, ZINC ION, ... (4 entities in total)
• Functional Keywords: fcho eps15 mu homology domain endocytosis, signaling protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm. Isoform 2: Early endosome membrane ; Peripheral membrane protein ; Cytoplasmic side : P42566
• Total number of polymer chains: 4
• Total formula weight: 68224.35

Authors

McCoy, A.J.,Wrobel, A.,Owen, D.J. (deposition date: 2016-05-03, release date: 2016-06-08, Last modification date: 2024-11-20)

Primary citation

Ma, L.,Umasankar, P.K.,Wrobel, A.G.,Lymar, A.,McCoy, A.J.,Holkar, S.S.,Jha, A.,Pradhan-Sundd, T.,Watkins, S.C.,Owen, D.J.,Traub, L.M.
Transient Fcho1/2Eps15/RAP-2 Nanoclusters Prime the AP-2 Clathrin Adaptor for Cargo Binding.
Dev.Cell, 37:428-443, 2016

PubMed Abstract: Clathrin-coated vesicles form by rapid assembly of discrete coat constituents into a cargo-sorting lattice. How the sequential phases of coat construction are choreographed is unclear, but transient protein-protein interactions mediated by short interaction motifs are pivotal. We show that arrayed Asp-Pro-Phe (DPF) motifs within the early-arriving endocytic pioneers Eps15/R are differentially decoded by other endocytic pioneers Fcho1/2 and AP-2. The structure of an Eps15/R⋅Fcho1 μ-homology domain complex reveals a spacing-dependent DPF triad, bound in a mechanistically distinct way from the mode of single DPF binding to AP-2. Using cells lacking FCHO1/2 and with Eps15 sequestered from the plasma membrane, we establish that without these two endocytic pioneers, AP-2 assemblies are fleeting and endocytosis stalls. Thus, distinct DPF-based codes within the unstructured Eps15/R C terminus direct the assembly of temporary Fcho1/2⋅Eps15/R⋅AP-2 ternary complexes to facilitate conformational activation of AP-2 by the Fcho1/2 interdomain linker to promote AP-2 cargo engagement.

PubMed: 27237791
DOI: 10.1016/j.devcel.2016.05.003

Experimental method

X-RAY DIFFRACTION (2.4 Å)